Federico Pessina, Pierina Navarria, Luisa Bellu, Elena Clerici, Letterio Salvatore Politi, Maria Pia Tropeano, Matteo Simonelli, Maurizio Fornari, and Marta Scorsetti
Coronavirus disease 2019 (COVID-19) has changed the way in which cancer is treated. Patients with high-grade glioma (HGG) are believed to be in a vulnerable category. The aim of this study was to describe the experience of a hub cancer center and the measures that were put in place for treatment of patients with newly diagnosed and recurrent glioma.
To prevent in-hospital contagion and preserve the safety of health professionals and patients, specific protocols and strict regulations were introduced. Physical distancing, use of surgical masks, and diligent hand hygiene were adopted. Each case was discussed in a multidisciplinary board meeting before treatment. All patient candidates for surgical procedures were tested for SARS-CoV-2 with a nasopharyngeal swab and a chest CT scan. Indications for surgery were the radiological suspicion of HGG in patients with a good performance status and/or the rapid and progressive occurrence of neurological deficits. Adjuvant treatments were performed only in cases of HGG. This therapy consisted of conventional fractional radiotherapy (RT; 60 Gy/30 fractions) with concomitant and adjuvant temozolomide chemotherapy (TMZCHT) in younger patients; in elderly patients, a short course of RT was employed (40.5 Gy/15 fractions). For recurrent HGG, treatments were assessed after a careful evaluation of the patient’s general condition, neurological status, and risk of early impairment in neurological status if not treated. During simulation CT for the RT plan, each patient underwent a chest CT study. In cases in which an imaging study was suspicious for COVID-19 pneumonia, the patient was immediately isolated and rapidly underwent nasopharyngeal swab testing.
Between March 1 and April 30, 2020, 23 HGGs were treated, and these cases are included in the present evaluation. Fifteen patients harboring newly diagnosed glioblastoma (GBM) underwent resection followed by a regimen of chemotherapy and RT, and 3 patients with newly diagnosed anaplastic oligodendroglioma underwent surgery followed by adjuvant RT. Five patients were treated for recurrent GBM, and they received surgery plus adjuvant RT. One patient in whom the simulation CT study was suspicious for COVID pneumonia was tested with a nasopharyngeal swab, which proved positive for SARS-CoV-2 infection. No patients contracted COVID-19 during hospitalization for surgery or during RT treatment. Corticosteroid therapy was administered to all patients beginning on the 1st day of RT.
The authors’ experience during the COVID-19 pandemic showed that patients with HGG can be treated in the most effective manner without a compromise in safety. Careful selection criteria and a multidisciplinary evaluation are pivotal to assessing the optimal therapeutic strategy.
Marco Rossi, Federico Ambrogi, Lorenzo Gay, Marcello Gallucci, Marco Conti Nibali, Antonella Leonetti, Guglielmo Puglisi, Tommaso Sciortino, Henrietta Howells, Marco Riva, Federico Pessina, Pierina Navarria, Ciro Franzese, Matteo Simonelli, Roberta Rudà, and Lorenzo Bello
Surgery for low-grade gliomas (LGGs) aims to achieve maximal tumor removal and maintenance of patients’ functional integrity. Because extent of resection is one of the factors affecting the natural history of LGGs, surgery could be extended further than total resection toward a supratotal resection, beyond tumor borders detectable on FLAIR imaging. Supratotal resection is highly debated, mainly due to a lack of evidence of its feasibility and safety. The authors explored the intraoperative feasibility of supratotal resection and its short- and long-term impact on functional integrity in a large cohort of patients. The role of some putative factors in the achievement of supratotal resection was also studied.
Four hundred forty-nine patients with a presumptive radiological diagnosis of LGG consecutively admitted to the neurosurgical oncology service at the University of Milan over a 5-year period were enrolled. In all patients, a policy was adopted to perform surgery according to functional boundaries, aimed at achieving a supratotal resection whenever possible, without any patient or tumor a priori selection. Feasibility, general safety, and tumor or patient putative factors possibly affecting the achievement of a supratotal resection were analyzed. Postsurgical patient functional performance was evaluated in five cognitive domains (memory, language, praxis, executive functions, and fluid intelligence) using a detailed neuropsychological evaluation and quality of life (QOL) examination.
Total resection was feasible in 40.8% of patients, and supratotal resection in 32.3%. The achievement of a supratotal versus total resection was independent of age, sex, education, tumor volume, deep extension, location, handedness, appearance of tumor border, vicinity to eloquent sites, surgical mapping time, or surgical tools applied. Supratotal resection was associated with a long clinical history and histological grade II, suggesting that reshaping of brain networks occurred. Although a consistent amount of apparently MRI-normal brain was removed with this approach, the procedure was safe and did not carry additional risk to the patient, as demonstrated by detailed neuropsychological evaluation and QOL examination. This approach also improved seizure control.
Supratotal resection is feasible and safe in routine clinical practice. These results show that a long clinical history may be the main factor associated with its achievement.
Pierina Navarria, Federico Pessina, Elena Clerici, Zefferino Rossini, Davide Franceschini, Giuseppe D’Agostino, Ciro Franzese, Tiziana Comito, Mauro Loi, Matteo Simonelli, Elena Lorenzi, Pasquale Persico, Letterio Salvatore Politi, Marco Grimaldi, Lorenzo Bello, Armando Santoro, Maurizio Fornari, Franco Servadei, and Marta Scorsetti
Anaplastic gliomas (AGs) are an extremely heterogeneous group of primary brain tumors. More recently, new discoveries have indicated that isocitrate dehydrogenase (IDH) mutation status is the most important parameter predicting survival. The primary aim of the present analysis was to identify prognostic factors, other than IDH status, that eventually impact survival.
Patients with available clinical, imaging, and molecular profile data who were amenable to resection were evaluated. The extent of resection (EOR) was defined as gross-total resection (GTR), near-total resection (NTR), subtotal resection (STR), or partial resection (PR). Residual tumor volume (RTV) was quantified. Following surgery, patients received adjuvant chemotherapy alone, radiation therapy plus concomitant and adjuvant temozolomide (TMZ), or sequential radio-chemotherapy. Clinical outcome was evaluated by neurological examination and MRI 1 month after treatment and every 4 months thereafter. Tumor progression was defined according to the Response Assessment in Neuro-Oncology (RANO) working group.
Among 402 patients referred to the authors’ institution for AG, 142 were included in the present analysis. Eighty-eight (62%) were male and 54 (38%) were female, with a median age of 43 years (range 19–70 years). At admission, most patients had a Karnofsky Performance Scale score of 90–100 (84.5%) and were symptomatic (93.7%). Forty-eight (33.8%) patients had newly diagnosed anaplastic oligodendrogliomas (AOs), and 94 (66.2%) had anaplastic astrocytomas (AAs). Most of them had mutant IDH tumors (67.6%) and methylated O
6-methylguanine-DNA-methyltransferase (MGMT) promoter status (71.8%). GTR was performed in more than half of the patients (56.3%). RTV was detected in 83 (58.5%) patients. Following surgery, 72 (50.7%) patients received radiotherapy with concomitant and adjuvant TMZ, 48 (33.8%) received sequential radio-chemotherapy, and 22 (15.5%) received adjuvant chemotherapy alone. The median follow-up time was 40 months (range 16–146 months). The median PFS time and the 1-, 3-, and 5-year PFS rates were 35 months (95% CI 27–76) and 78.9% ± 3.4%, 49.7% ± 4.6%, and 42.7% ± 5.4%, respectively. The median OS time and the 1-, 3-, and 5-year OS rates were 91 months (95% CI 66–95) and 90.1% ± 2.5%, 70.9% ± 4.2%, and 61.8% ± 4.9%, respectively. Prognostic factors predicting survival other than molecular profile were the EOR and the RTV (p < 0.0001). Sequential radio-chemotherapy was the more effective treatment administered.
In addition to IDH status, EOR and the RTV have proved to statistically impact survival. The pivotal role of adjuvant radiotherapy has been recorded in all AG patients, regardless of tumor features.